Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world, causing serious adverse events on women's reproductive health including complications of pregnancy, pelvic inflammatory disease and infertility. The objectives of this project are to define the epidemiology, risk factors, transmission kinetics, and pathogenesis of C. trachomatis infections in different population settings, including populations in resource constrained countries. In a multi-center international trial of 5,000 participants, we screened for a variety of STDs using non-invasive molecular amplified assays. Prevalence of chlamydia in young women was 12.2% in China, 0.1% in India, 6.4% in Peru, 10.4% in Russia, and 2.5% in Zimbabwe. Serologic evidence for HSV-2 infection ranged from 9 to 59%. These data have important implications for the future of the HIV epidemics because of the strong association of STDs, particularly HSV-2 for HIV acquisition. We have used the Internet to offer sampling in the U.S. for chlamydia for >2400 women at home using self-obtained vaginal swabs, which were reported to be highly acceptable. Prevalence has been 15.3% in young women age 15-19 yr. Both young age and Black ethnicity were statistically associated with chlamydia positivity. We have extended Internet screening to over 800 males with self-collected penile swabs and urines. Over 21% were positive for at least one STD with acceptance for collecting penile swabs being high and the numbers of STDs detected was higher than in urine. 77% of men preferred a self-administered penile specimen versus attending a clinic, 89% reported collection of a penile swab was easy, and 89% would use internet-based screening again. A program for self-collected rectal swabs obtained at home was recently added to the Internet screening. This unique public health strategy can provide increased screening outside the traditional STD or Family Planning Clinic. We have documented a decrease in the prevalence of both chlamydia and gonorrhea in a community out- reach program for pregnant women in Baltimore. In 1999 the prevalence of chlamydia was 18.2% but declined over the subsequent years to 10.2% in 2010. Continuation of outreach screening and treatment programs can help reduce the prevalence of STDs in our community. We participated in surgical and antibiotic treatment intervention studies in Ethiopia, Niger, and Tanzania in efforts to control trachoma, the most common infectious cause of blindness worldwide. These studies have shown dramatic reductions in blindness in communities in which severe disease is first treated with surgery followed by community-wide azithromycin mass therapy. To determine whether infection recurs, we re-examined individuals in Tanzania five years after initiation of the program. Treatment coverage was 80% for all ages in the first year, although coverage 18 months later was lower at <70%. At five years, clinical trachoma rates were still lower than at baseline, ranging from 45% compared to 81% at baseline. Chlamydia infection rates at baseline were 71%, but declined to 27% five years after two rounds of mass therapy. In a sub-study of the Tanzania program, we studied the ancillary benefits of azithromycin in affecting chlamydia, gonorrhea, malaria, respiratory infections, and diarrhea. The prevalence of genital infections caused by C. trachomatis was 4.2% at baseline before therapy in the Intervention (mass therapy) villages and 2.2% in the control villages. Mass therapy with azithromycin for trachoma in the intervention communities decreased both chlamydia and gonorrhea prevalence below baseline at one month and at 6 months. We plan to continue the mass treatment of villages in Tanzania to determine the frequency of treatment in relationship to control of ocular infections.